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A Multicenter Phase 2 Single-arm Proof-of-concept Trial Assessing the Efficacy and Safety of Obinutuzumab in the Treatment of Non-infectious Active Cryoglobulinemia Vasculitis Refractory or Intolerant to Rituximab

NCT07268521 · Status: NOT_YET_RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 30

Last updated 2025-12-05

No results posted yet for this study

Summary

Cryoglobulinemic vasculitis (CV) is a rare life threatening systemic immune-complex-mediated vasculitic syndrome. Symptoms range from arthralgia, purpura to more severe manifestations such as peripheral neuropathy, glomerulonephritis, and skin necrosis.1 CV is associated with significant morbidity and mortality. The management of non-infectious mixed CV is currently based on steroids, and anti-CD20 monoclonal antibody Rituximab (RTX). Infectious complications of immunosuppressants (IS) remain the main cause of death in CV. During the last decade, studies reported efficacy of RTX in patients with CV in 65-70% of patients as compared to 30% for other IS (azathioprine…). However, CV relapse is noted in up to 40% patients within few days to 19 months after the last RTX infusion2. Following RTX, serum levels of B lymphocyte stimulator (BLyS) significantly increased and may favour the survival of autoreactive B cell clones and relapses of CV. A recent study has shown that RTX does not reset defective early B cell tolerance checkpoints. Incomplete B cell depletion following treatment with RTX may be associated with poor clinical response.

Moreover, some patients develop a serum sickness reaction to RTX that contraindicate further use of the medication2. Thus, there are important therapeutic unmet needs in CV patients that are refractory or intolerant to RTX.

Obinutuzumab (OBZ) is a type II anti-CD20 monoclonal antibody with a glycomodified Fc, approved in 2013 for the treatment of chronic lymphocytic leukemia. Reddy et al. found that OBZ was at least 2-fold more efficient than RTX at inducing B-cell cytotoxicity in in vitro whole blood assays of patients with rheumatoid arthritis and systemic lupus erythematosus. In lupus nephritis, OBZ resulted in increased complete and partial renal responses compared with placebo when added to mycophenolate mofetil and steroids for the treatment of lupus nephritis. There is a strong rationale for using OBZ in CV. OBZ is currently used off label in CV patients intolerant to RTX and case reports pointed out its effectiveness in CV4.5. CRYOBI is the first prospective multicenter phase 2 proof-of-concept trial assessing efficacy of OBZ in CV refractory or intolerant to RTX.

Conditions

  • Cryoglobulinemic Vasculitis (CV)

Interventions

DRUG

Obinutuzumab

Obinutuzumab will be administered intravenously at 1000 milligrams (mg) at week 0 and week 2

Sponsors & Collaborators

  • Assistance Publique - Hôpitaux de Paris

    lead OTHER

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-12-01
Primary Completion
2028-04-01
Completion
2028-09-01

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Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07268521 on ClinicalTrials.gov